title: Extrasynaptic delta-containing GABAA receptors in the nucleus accumbens dorsomedial shell contribute to alcohol intake.
abstract: Recent findings suggest that extrasynaptic δ-subunit-containing GABA(A) receptors are sensitive to low-to-moderate concentrations of alcohol, raising the possibility that these receptors mediate the reinforcing effects of alcohol after consumption of one or a few drinks. We used the technique of viral-mediated RNAi to reduce expression of the GABA(A) receptor δ-subunit in adult rats in localized regions of the nucleus accumbens (NAc) to test the hypothesis that δ-subunit-containing GABA(A) receptors in the NAc are necessary for oral alcohol consumption. We found that knockdown of the δ-subunit in the medial shell region of the NAc, but not in the ventral or lateral shell or in the core, reduced alcohol intake. In contrast, δ-subunit knockdown in the medial shell did not affect intake of a 2% sucrose solution, suggesting that the effects of GABA(A) receptor δ-subunit reduction are specific to alcohol. These results provide strong evidence that extrasynaptic δ-subunit-containing GABA(A) receptors in the medial shell of the NAc are critical for the reinforcing effects of oral ethanol.
authors.affiliation: Ernest Gallo Clinic and Research Center, University of California, Emeryville, CA 94608, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Nie
authors.forename: Mridula
authors.initials: M
authors.lastname: Rewal
authors.forename: T Michael
authors.initials: TM
authors.lastname: Gill
authors.forename: Dorit
authors.initials: D
authors.lastname: Ron
authors.forename: Patricia H
authors.initials: PH
authors.lastname: Janak
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000284:Administration, Oral; D000428:Alcohol Drinking / Q000378:metabolism*; D000818:Animals; D055785:Gene Knockdown Techniques; D008297:Male; D020645:Mediodorsal Thalamic Nucleus / Q000378:metabolism* / Q000473:pathology; D009714:Nucleus Accumbens / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D015203:Reproducibility of Results; D013395:Sucrose / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011963:Receptors, GABA-A; D013395:Sucrose